Polycystic ovary syndrome (PCOS) Flashcards
Define polycystic ovary syndrome (PCOS).
A heterogeneous endocrine disorder that appears to emerge at puberty.
Includes:
- symptoms of hyper-androgenism,
- presence of hyper-androgenaemia,
- oligo-/anovulation,
- and polycystic ovarian morphology on ultrasound
What are the clinical features of PCOS?
Clinical features vary widely
What is the aetiology of PCOS?
Unknown
Insulin resistance and consequent compensatory hyperinsulinaemia are key factors. Hyperinsulinaemia then causes:
- Reduced SHBG -so more testosterone in biologically active unbound form is available
- Increased androgen producttion which stops follicular development and causes anovulation amd menstrual disturbance
- Weight gain due to insulin resistance
Hormonal imbalance is common
- LH elevated due to increased amplitute and frequency of LH pulses
- Theca cells of ovary produce excess androgens due to hyperinsulinaemia/high LH. Theca cells in PCOS are more efficient at converting androgens to testosterone
- Serum oestrogen levels raised as follicular development stops at a stage short of full maturity of the ovulatory follicle so there is no oestrogen deficiency and no progestogen so endometrium becomes hyperplastic. Excess oestrogen may also be converted to testosterone in peripheral fat.
Genetic link in some cases but no specific genes identified
What are some risk factors for PCOS?
- FH of PCOS
- Premature adrenarche
- Obesity - having PCOS does not appear to increase risk of obesity
How common is PCOS?
1 in 10 - many undiagnosed
Single most common cause of infertility in young women
Most common endocrinopathy in women of reproductive age
What are the clinical features of PCOS?
- subfertility and infertility
- menstrual disturbances: oligomenorrhea and amenorrhoea
- hirsutism, acne (due to hyperandrogenism)
- obesity
- acanthosis nigricans (due to insulin resistance)
What investigations should be done for PCOS?
Bloods:
- Calculate free androgen index - normal or elevated
- FSH, LH - measure to rule out premature ovarian insufficiency etc.
- TSH - exclude hypothyroidism
- Prolactin - exclude hyperprolactinaemia
Imaging:
- US - multiple cysts on ovaries. Ultrasound scan should not be used for the diagnosis of PCOS in adolescents due to the high incidence of multi-follicular ovaries in this life stage.
What does the free androgen index show? What is it in PCOS?
Used to caculate physiologically active testosterone level
100 x total testosterone / SHBG level
Normal or elevated in PCOS
Normal is <5
If testosterone is twice upper limit of normal/>5nmol/L, should you suspect PCOS?
No suspect other causes e.g. andorgen-secreting tumour or CAH
What is the conservative management (advice and screening) of PCOS?
Inform of possible long-term complications
Advise on measures to reduce CVD risk, including diet, exercise, and where appropriate, weight loss and smoking cessation.
Offer screening for IGT/T2DM (2 hour post 75g OGTT), CVD risk factors (QRISK2 assessment tool).
Check BP for HTN
Regular monitoring
What are the benefits of weight loss in PCOS?
Explain that weight loss may:
- Reduce hyperinsulinism and hyperandrogenism.
- Reduce the risk of type 2 diabetes and CVD.
- Result in menstrual regularity.
- Improve the chance of pregnancy (if it is desired).
What is the management of oligomenorrhoea/amenorrhoea in PCOS?
- Cyclical progestogen e.g. medroxyprogesterone 10 mg daily for 14 days every 1–3 months. This helps prevent endometrial hyperplasia.
- Low-dose COC
- LNG-IUS
What is the management of acne in PCOS?
COC - 1st line
+/- topical retinoids, topical/oral antibiotics
What is the management of hirsutism in PCOS?
- Lifestyle changes - weight loss may reduce hyperandrogenism; shaving and waxing
- Topical eflornithine cream - ameliorates hirsutism
- COC - but more effective for acne than hisrsutism; modestly inhibits gonadotrophin secretion + increases SHBG to decrease testosterone
- Anti-androgens e.g. spironolactone, flutamide, cyproterone, finasteride. Used for severe hisrsutism.
- GnRH analogues e.g. leuprorelin in very severe ovarian hyper-androgenism
What is the management of infertility in PCOS?
- Lifestyle changes - weight loss if overweight will improve chances of pregnancy, avoid smoking.
- Metformin - if weight loss is unsuccessful; may restore menses/ovulation to the point that conception is possible
- Letrozole or clomifene - induce ovulation/anti-oestrogen; letrozole for all women or clomifene if BMI>30kg/m2. Letrozole is an aromatase inhibitor (prevents conversion of androgens to oestrogens).
- Consider referral for fertility treatment e.g. IVF
Which surgical treatment may help restore fertility in PCOS?
Laparoscopic ovarian drilling - procedure that destroys the ovarian stroma and may prompt ovulatory cycles
What is a risk associated with clomifene? How does it work?
There is a potential risk of multiple pregnancies with anti-oestrogen* therapies such as clomifene
*work by occupying hypothalamic oestrogen receptors without activating them. This interferes with the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion
What are some important symptoms to screen for in PCOS which may require further investigation?
Obstructive sleep apnoea - ask about snoring and daytime fatigue/somnolence
Emotional wellbeing - PCOS may cause negative views of body image, psychosexual problems and loss of feminine identity, eating disorders.
What are the complications of PCOS?
- Metabolic disorders - insulin resistance in 65-80%, T2DM, IGT
- Cardiovascular disease - more risk factors for this including central obesity, high TG, low HDL, HTN.
- NAFLD - in 40-55%; 10% of these develop NASH and of these 20% progress to cirrhosis
- Infertility
- Pregnancy complications - gestational diabetes, HTN, pre-eclampsia (x4), premature delivery (x2), miscarriage, C-section.
- Endometrial cancer - risk due to prolonged oligomenorrhoea/amenorrhoea (x3 compared to normal).
- Psychological - higher risk of depression, anxiety, eating disorders, sexual and relationship dysfunction
- Obstructive sleep apnoea
What is the prognosis with PCOS?
Chronic condition with no cure but goal is to treat to alleviate signs/symptoms and prevent complications.
What other causes of hyperandrogenism must be ruled out before PCOS diagnosis?
- CAH
- Cushing’s syndrome
- Androgen-secreting tumour
What other causes of oligomenorrhoea/amenorrhoea must be ruled out before diagnosis of PCOS?
- premature ovarian failure - raised LH and FSH and decreased in hypogonadotrophic hypogonadism
- hypothyroidism
- hyperprolactinaemia - although in PCOS prolactin mey be mildly elevated
What is the definition of polycystic ovaries? Do these have to be present for PCOS diagnosis?
Polycystic ovaries on US are defined as:
- the presence of _>_12 or more follicles in at least one ovary (measuring 2–9 mm diameter)
- or increased ovarian volume (greater than 10 cm3)
Do not have to be present to make the diagnosis and the finding of polycystic ovaries does not alone establish the diagnosis.
What is IGT?
Plasma glucose of 7.8mmol/L or more but <11.1mmol/L after 2-hour OGTT of 75g
